Clinically important drug interactions occur essentially at two levels, at the pharmacokinetic level and at the pharmacodynamic level. This chapter describes the clinically significant interactions between antiepileptic drugs (AEDs) and non-AEDs. The interactions can be classified into three groups according to their risk of interaction with AEDs. Carbamazepine is a potent hepatic enzyme inducer and, as well as inducing its own metabolism via an action on CYP3A4, it also induces the metabolism of many other drugs that are CYP3A4 substrates. There are no clinical data to suggest ethosuximide induces or inhibits the metabolism of other non-AEDs. As a new AED, knowledge of the interaction profile of felbamate with non-AEDs is limited. Zonisamide undergoes extensive metabolism, via CYP3A4, and approximately 30% of zonisamide is excreted in urine as unchanged zonisamide. To date, there are no reports of zonisamide affecting the pharmacokinetics of non-AEDs.